Localized aggressive periodontitis (LAP) affects 70,000 US children, largely from underserved communities. If untreated social and psychological stigma resulting from tooth loss can occur. This study is designed to identify early markers of aggressive periodontitis (eMAPs). Risk markers that include Aggregatibacter actinomycetemcomitans (Aa), other microbes, and host response elements will be examined over time. Adolescents will be screened to select a balanced cohort of 250 Aa-positive and 250 Aa-negative periodontally healthy students who will be enrolled and followed for 2 years. The purpose of this study is to detect microbial and host biomarkers that precede clinical evidence of bone loss (BL) with the aim of developing a chair-side diagnostic system for rapid identification of susceptible subjects. Thus far, we have developed a test that permits immediate chair-side identification of subjects with Aa, and a test for chemokines related to BL. However, our data indicates that Aa alone is not sufficient for diagnosis, and macrophage inflammatory protein 1-alpha (MIP-1?) while novel and related to BL can be improved upon by finding markers that identify earlier events. Clinical measurements and sampling of buccal epithelial cells (BECs), saliva, plaque, and crevice fluid will be performed every 3 months. Stored samples will be analyzed prospectively to assess host and microbial biomarkers (salivary, crevicular and microbial elements) that predate BL (Aa and MIP-1?) and predict bone loss in a subject (AIM 1a) and at a site (AIM 1b), and then to retrospectively determine new biomarkers that predate BL when a subject (AIM 2a) and a site develops radiographic signs of BL (AIM 2b). AIM 1a assesses whether Aa on buccal cells in combination with salivary MIP-1?an osteoclast promoter, can serve as predictive diagnostic markers for individuals who will develop LAP. AIM 1b assesses levels of: 1) the proposed antagonists (a consortium of subgingival bacteria including Aa, S. parasanguinis and F. alocis), and 2) host response element (crevicular MIP-1? as predictive markers of time-dependent risk for BL at a tooth sites within 6-9 months. AIM 2 examines host and microbial markers that appear earlier than markers tested in AIM 1. After detection of BL, samples taken 3, 6, 9, and 12 months earlier will be tested for salivary and microbial factors that could promote colonization of the consortium on BECs at the subject level (AIM 2a). At the site level we will study the orchestration and timing of individual bacteria that make up the subgingival LAP consortium to determine if previously undetected bacteria (using NextGen sequencing) may also be involved in disease initiation. Further, sequential timing of early, middle, and late host cytokines as they appear in crevice fluid will be analyzed to identify biomarkers (AIM 2b) appearing at a BL site in advance of markers studied in AIM 1. Our premise is that the knowledge gained can provide sensitive and specific biomarkers that can supplant diagnostic tools used currently in practice. In this manner, subjects at risk can be identified in the earliest stages of disease so that cost-effective strategies can be instituted to reduce oral health disparities.